Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

Shang, Yueli; Yang, Xiaojing; Zhang, Rui; Zou, Huafeng; Zhao, Ruqian

doi:10.1007/s00726-011-0907-1

Cited by 21 publications

(12 citation statements)

References 49 publications

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“…Downregulation of miR-498 was also found in the nasal mucosa of allergic rhinitis patients [64]. In addition, miR-498 was has recently been reported to play a possible role in translational repression of 11β-hydroxysteroid dehydrogenase type 2 mRNA in BeWo cells (human placental cell line) subjected to amino acid deficiency [65]. However, in our study, miR-498 and miR-320d played an important role in regulating KSHV replication.…”

Section: Discussioncontrasting

confidence: 43%

Cellular MicroRNAs 498 and 320d Regulate Herpes Simplex Virus 1 Induction of Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication by Targeting RTA

et al. 2013

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Kaposi’s sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for KS development without other cofactors. We have previously reported that herpes simplex virus (HSV)-1 was an important cofactor that reactivated KSHV from latency by inducing the expression of KSHV replication and transcription activator (RTA), the lytic switch protein. Here, we further investigated the possible cellular microRNAs (miRNAs) involved in regulation of RTA during HSV-1-induced KSHV replication. The differential profiles of miRNAs expression between Mock- and HSV-1-infected body cavity-based lymphoma (BCBL-1) cells were identified by miRNA microarray analysis. Bioinformatics and luciferase reporter analyses showed that two of the HSV-1-downregulated cellular miRNAs, miR-498 and miR-320d, directly targeted the 3′ untranslated region (UTR) of KSHV RTA. As a result, overexpression of these two miRNAs significantly inhibited HSV-1-induced KSHV replication, whereas repression of these miRNAs with specific suppressors enhanced HSV-1-mediated KSHV replication. In addition, miR-498 or miR-320d alone, without HSV-1 infection, regulated KSHV replication in BCBL-1 cells. Finally, bioinformatics Gene Ontology (GO) analysis indicated that targets of HSV-1-regulated miRNAs were enriched for proteins, whose roles were involved in protein binding, enzyme activity, biological regulation, and several potential signaling pathways including transforming growth factor (TGF)-β were likely to participate in HSV-1-induced KSHV replication. Collectively, these novel findings demonstrated that host-encoded miR-498 and miR-320d regulated HSV-1 induction of KSHV lytic replication by targeting RTA, which provided further insights into the molecular mechanisms controlling KSHV lytic replication.

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Section: Discussioncontrasting

confidence: 43%

Cellular MicroRNAs 498 and 320d Regulate Herpes Simplex Virus 1 Induction of Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication by Targeting RTA

et al. 2013

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“…34 Shang et al 34 starved a human placental cell line (BeWo) from amino acids and observed a decline in the 11β-HSD2 activity, which was unexplained by a change in HSD11B2 mRNA abundance. The authors checked the expression of 5 different miRNAs for potential underlying mechanisms and found a significant increase in miR-498 level after cellular starvation.…”

Section: Discussionmentioning

confidence: 99%

“…How the miRNAs were selected for testing was not reported. 34 By using 3 miRNA target prediction programs (described above), we identified a weak prediction for miR-498 binding to the 3′-UTR of HSD11B2 only by miRanda. In our analysis of CCDs, miR-498 was not identified.…”

Section: Discussionmentioning

confidence: 99%

“…17 CpG methylation again depends on a variety of enzymes. 36 Although several promising miRNA candidates relevant for the expression of an individual protein or a complex disease state have been reported, 32,34,37,38 it seems that for physiological reasons, a pattern of miRNAs rather than an individual miRNA might govern the expression of a protein at its site of action. Therefore, we isolated the physiologically most relevant tissue for 11β-HSD2 action, the CCD, for the assessment of miRNA profile and compared this profile with that of the PCT that is virtually devoid of 11β-HSD2 activity (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

et al. 2014

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Abstract-The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. A diminished activity causes salt-sensitive hypertension. The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) expression in the cortical collecting duct is poorly understood. Here, we analyzed for the first time whether the 11β-HSD2 expression is modulated by microRNAs (miRNAs). In silico analysis revealed 53 and 27 miRNAs with potential binding sites on human or rat HSD11B2 3′-untranslated region. A reporter assay demonstrated 3′-untranslated region-dependent regulation of human and rodent HSD11B2. miRNAs were profiled from cortical collecting ducts and proximal convoluted tubules. Bioinformatic analyses showed a distinct clustering for cortical collecting ducts and proximal convoluted tubules with 53 of 375 miRNAs, where 13 were predicted to bind to the rat HSD11B2 3′-untranslated region. To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with saltsensitive hypertension.(1) Comparing Sprague-Dawley with low and Wistar rats with high 11β-HSD2 activity revealed rno-miR-20a-5p, rno-miR-19b-3p, and rno-miR-190a-5p to be differentially expressed. (2) Uninephrectomy lowered 11β-HSD2 activity in the residual kidney with differentially expressed rno-miR-19b-3p, rno-miR-29b-3p, and rnomiR-26-5p. In conclusion, miRNA-dependent mechanisms seem to modulate 11β-HSD2 dosage in health and disease The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl

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“…[13]. Numerous reports have indicated that 11β-HSD2 can be regulated by MAPKs signalling [32], [33]. Furthermore, MAPKs have been proven to modify GC sensitivity, namely that the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK reduce and enhance GC sensitivity, respectively [16].…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by Bortezomib Sensitizes Jurkat Leukemia T Cells against Glucocorticoid-Induced Apoptosis

Wang

et al. 2013

PLoS ONE

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11β-hydroxysteroid dehydrogenases type 2 (11β-HSD2), a key regulator for pre-receptor metabolism of glucocorticoids (GCs) by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion) through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

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Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

Cited by 21 publications

References 49 publications

Cellular MicroRNAs 498 and 320d Regulate Herpes Simplex Virus 1 Induction of Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication by Targeting RTA

Cellular MicroRNAs 498 and 320d Regulate Herpes Simplex Virus 1 Induction of Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication by Targeting RTA

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

Down-Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by Bortezomib Sensitizes Jurkat Leukemia T Cells against Glucocorticoid-Induced Apoptosis

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